US6652479B2 - Method and apparatus for transcutaneous infusion of carbon dioxide for local relief of pain and other ailments - Google Patents

Method and apparatus for transcutaneous infusion of carbon dioxide for local relief of pain and other ailments Download PDF

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US6652479B2
US6652479B2 US09/795,648 US79564801A US6652479B2 US 6652479 B2 US6652479 B2 US 6652479B2 US 79564801 A US79564801 A US 79564801A US 6652479 B2 US6652479 B2 US 6652479B2
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skin
carbon dioxide
application
subject
gas
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US20020040205A1 (en
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Ned S. Rasor
Julia S. Rasor
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Soleno Therapeutics Inc
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Capnia Inc
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Assigned to CAPNIA, INCORPORATED reassignment CAPNIA, INCORPORATED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: RASOR, NED S.
Assigned to CAPNIA, INCORPORATED reassignment CAPNIA, INCORPORATED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: RASOR, JULIA S.
Publication of US20020040205A1 publication Critical patent/US20020040205A1/en
Priority to US10/666,562 priority patent/US20080132825A1/en
Priority to US10/666,947 priority patent/US20050228337A1/en
Publication of US6652479B2 publication Critical patent/US6652479B2/en
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Assigned to CAPNIA, INC. reassignment CAPNIA, INC. CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME AND TO UPDATE THE ASSIGNEE ADDRESS PREVIOUSLY RECORDED ON REEL 011901 FRAME 0234. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNEE NAME IS CAPNIA, INC. AND THE ASSIGNEE ADDRESS IS 2445 FABER PLACE, SUITE 250, PALO ALTO, CA 94303. Assignors: RASOR, JULIA S.
Assigned to CAPNIA, INC. reassignment CAPNIA, INC. CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME AND TO UPDATE THE ASSIGNEE ADDRESS PREVIOUSLY RECORDED ON REEL 011901 FRAME 0247. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNEE NAME IS CAPNIA, INC. AND THE ASSIGNEE ADDRESS IS 2445 FABER PLACE, SUITE 250, PALO ALTO, CA 94303. Assignors: RASOR, NED S.
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H33/00—Bathing devices for special therapeutic or hygienic purposes
    • A61H33/14—Devices for gas baths with ozone, hydrogen, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
    • A61M15/0033—Details of the piercing or cutting means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/009—Inhalators using medicine packages with incorporated spraying means, e.g. aerosol cans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H33/00—Bathing devices for special therapeutic or hygienic purposes
    • A61H33/14—Devices for gas baths with ozone, hydrogen, or the like
    • A61H2033/145—Devices for gas baths with ozone, hydrogen, or the like with CO2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0065—Inhalators with dosage or measuring devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/02—Gases
    • A61M2202/0225—Carbon oxides, e.g. Carbon dioxide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/06—Solids
    • A61M2202/064—Powder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2210/00—Anatomical parts of the body
    • A61M2210/06—Head
    • A61M2210/0618—Nose

Definitions

  • This invention relates to methods and apparatus for delivery of carbon dioxide (CO 2 ), and other physiologically active agents to individuals.
  • CO 2 carbon dioxide
  • the present invention relates to methods and apparatus for transcutaneous application of CO 2 (i.e., applied to the skin) and transmucosal application of CO 2 (i.e., applied to a mucous membrane) in both the form of a gas and in the form of aqueous solutions (such as carbonated water).
  • CO 2 is a known therapeutic agent and subcutaneous application has been found to relieve a variety of ailments.
  • Cervico-cranial syndrome in particular pains in the neck, contractions of the neck, headache including migraine and vertigo;
  • the treatments consisted of daily or twice-weekly injections of 100-200 ml of CO 2 gas under the skin, in the body regions indicated, for a period of 2-5 weeks (10-15 injections).
  • 171 became difficulty-free or were substantially improved, 157 were improved with some remaining distress and 7 had no improvement.
  • Effervescent mineral water baths have been known from antiquity to the present as being effective for relieving musculoskeletal, neural and rheumatic pain. In general, it has been assumed that the dissolved mineral components were responsible for the therapeutic effects of the baths. However, the experimental evidence developed by the inventors suggests that the effectiveness of such baths arises from the high CO 2 content of the mineral water rather than from its other dissolved components.
  • results similar to those obtained by subcutaneous injection of CO 2 could be obtained by transcutaneous application of CO 2 .
  • This application could be made either by applying the CO 2 in the form of gas, or alternatively, in the form of aqueous solutions (i.e., carbonated water).
  • CO 2 may be transcutaneous (through the skin) or transmucosal (through a mucous membrane).
  • gaseous CO 2 or an aqueous solution of CO 2 may be applied to external skin surfaces for relief of various ailments.
  • an aqueous solution of CO 2 may be sprayed into the nose, mouth and/or upper respiratory passages for relief of various ailments as an alternative to the application of gaseous CO 2 which was described in U.S. patent applications Ser. No. 09/614,389 and 09/708,186.
  • FIG. 1 shows a device used to test absorption of carbon dioxide.
  • FIG. 2 shows the carbon dioxide absorbed by a wet paper towel in an experiment using the device of FIG. 1 .
  • FIG. 3 shows the device of FIG. 1 used on a human subject.
  • FIG. 4 shows a device for applying carbonated water to a selected portion of a subject's external skin surface.
  • FIG. 5 shows a subject utilizing a spray bottle containing carbonated water.
  • FIG. 6 shows a device used for obtaining a quantitative measurement of absorption of carbon dioxide in carbonated water through the skin of a human subject.
  • FIG. 7 shows the results of an experiment using the device of FIG. 6 .
  • FIG. 8 shows the results of the same experiment as in FIG. 7, but taken immediately after the subject had been exercising.
  • FIG. 9 shows the results of the experiment of FIG. 8 fifteen minutes after the measurements shown in FIG. 8 .
  • FIG. 10 shows a therapeutic application of gaseous carbon dioxide to an affected area of a subject.
  • FIG. 11 shows another therapeutic application of gaseous carbon dioxide to an affected area of a subject using a cup device.
  • FIG. 12 shows a subject submerging an affected body part into carbonated water.
  • FIG. 13 shows embodiments of “patches” for application of liquid or gaseous CO 2 .
  • Transcutaneous application of gaseous CO 2 has been found to relieve ailments previously treatable by subcutaneous injections of gaseous CO 2 .
  • FIG. 1 The apparatus and method employed for measuring the rate of CO 2 absorption by a surface is illustrated in FIG. 1 .
  • the device was placed on a table top 150 , and comprised a source of CO 2 in the form of a cylinder 101 and a flow regulator 110 , including a pressure regulator 112 and flow meter 113 .
  • Polyethylene tubing 115 of approximately 0.2 cm 2 lumen connected the cylinder 101 to a glass funnel 120 having a maximum area of 80 cm 2 .
  • An additional length of tubing 125 was used for measurement of changes in gas volume.
  • This gas volume measurement means used in the experiment could be eliminated in a device intended to administer CO 2 to a patient's skin surface.
  • the entire system was purged of air by prolonged CO 2 flow.
  • the additional length of tubing 125 was purged first, then a bolus of low-volatility (forepump) oil 130 was inserted into its open end and the end plugged.
  • the funnel 120 was then purged with its open end resting on a portion of the selected test surface 140 immediately adjacent to the portion to be tested, and with the purge flow escaping at its edge. At zero time the purge flow was terminated, the plug in the tube 125 end was removed and the funnel was slid onto the test portion of the surface without breaking the seal between the funnel edge and the wet surface.
  • the system was first tested by placing the funnel 120 on a non-absorbing test surface 140 without water. No movement of the bolus 130 occurred, which indicated that there was no significant absorption or evolution of gas within the system.
  • FIG. 2 shows the observed rate of absorption of gaseous CO 2 into the surface of the towel, i.e., a monotonic quasi-exponential approach of the absorbed gas volume to the amount apparently required to saturate the water in the towel with CO 2 .
  • the near linearity of the second (logarithmic) plot in FIG. 2 shows that the volume of gas changes quasi-exponentially as saturation is approached.
  • the observed initial rate of absorption determined from several such tests fell in the range 0.6-1.2 ml/min, and saturation occurred at 4-10 ml, for the 80-cm 2 area test surface.
  • the vascular bed of the skin suppresses saturation by removing CO 2 as fast as it diffuses into the skin, these rates would suggest that a 100-200 cc transcutaneous dose CO 2 would be delivered in 11 ⁇ 2 to 51 ⁇ 2 hours.
  • the inventors thus concluded that the rate was sufficient for a “CO 2 patch” to be feasible.
  • the time constant for the exponential saturation was found to be about three to five minutes, which was about the same as the reported time for disappearance of the gas emphysemum in the previously described subcutaneous gaseous CO 2 injections.
  • the experiment employed an open-cylinder procedure shown in FIG. 4 .
  • the interior diameter of the cylinder 410 measured approximately 5 cm.
  • the cylinder was placed over the area of localized pain on one thigh 420 .
  • the cylinder was then filled approximately 2 cm deep with carbonated water 430 .
  • the area of application was observed to be reddened to the degree described above in the Preliminary Experiments section when gaseous CO 2 was applied to the skin.
  • a PVC pipe was used as the cylinder, although in practice other materials could be used, provided that the resulting device was able to hold the water in position over the treatment area for the desired time.
  • carbonated water baths may be used effectively for treatment of musculoskeletal, neural and other rheumatic pains by immersion of the affected portions of the body or the whole body into fresh carbonated water for at least three minutes.
  • a capnic solution might be effective for treatment of upper respiratory indications for which infusion of gaseous CO 2 is effective.
  • a 70-ml commercially marketed plastic “squeeze” bottle 510 for dispensing a physiological saline spray was 3 ⁇ 4 filled with fresh effervescing carbonated water.
  • the carbonated water spray was then sprayed into the nose of a subject 520 who was suffering a mild allergic rhinitis attack. The inflammation and allergic distress were relieved immediately in a manner similar to that found when gaseous CO 2 was infused into the subject's nose.
  • the spray injection treatment is highly disagreeable compared with the gas infusion treatment and is no more effective.
  • the disagreeable aspects cited were the discomfort associated with a liquid being sprayed up the nose and the messiness of the effluent liquid from the nose after the spray.
  • the carbonated nasal spray is a distinct alternative for treatment of the upper respiratory distress indications, and shares many of the advantages of a gaseous CO 2 infusion treatment including effectiveness, ease of use, rapid relief on demand, unlimited dose, low cost, and freedom from aftereffects and other contraindications associated with the use of drugs. It is also possible to use the carbonated spray orally to deliver the dose of carbon dioxide to the mucous membranes in a similar manner.
  • the carbonated spray may offer superior treatment for patients suffering from dry nasal membranes along with allergy symptoms, i.e., the conditions for which the several saline nasal spray products presently are marketed.
  • a buffered isotonic solution should be used to minimize tissue volume changes by osmosis, but the solution should be carbonated by dissolving the maximum amount of CO 2 in it that is consistent with a practical operating pressure.
  • the inventors found that the degree of carbonation of commercially marketed carbonated water corresponds to an acceptable CO 2 pressure in the spray bottle (1-2 lb/in 2 at room temperatures). Furthermore, it has been found that the carbonated water can be stored for an indefinitely long period when the screw cap (not shown) of the dispenser 510 is tightly closed. Multiple effective doses of the spray are obtained until almost complete exhaustion of the spray bottle contents.
  • the inventors also undertook an experiment to obtain a quantitative indication of the extent and effect of transcutaneous infusion of CO 2 effected by applying a capnic aqueous solution (carbonated water) to the skin.
  • a capnic aqueous solution carbonated water
  • the inventors used a cylinder 605 of about 5 cm interior diameter, similar to that shown in FIG. 4, to apply about 2 cm of the capnic solution 610 to a subject's anterior thigh 620 .
  • the inventors then measured, using a digital logger 650 , the resulting electrical potential difference between the liquid and the subject's body.
  • the potential difference was measured between a stainless steel electrode 630 , immersed in a liquid pool (e.g. capnic solution) applied to the skin of the anterior thigh, and a large (15 ⁇ 25 cm) aluminum plate 640 (as indifferent electrode) applied to the moistened skin of the posterior thigh 620 .
  • a liquid pool e.g. capnic solution
  • FIGS. 7-9 show the changes in body/liquid potential difference after distilled water and carbonated water were applied simultaneously to adjacent regions of the skin of the anterior thigh.
  • Both carbonated water and distilled water electrodes are spontaneously positive relative to the body electrode, i.e., such as to inhibit transport of carbonate or bicarbonate ions into the body from the capnic solution, or to expel them from the body into the distilled water.
  • the carbonated water potential and its change with time always are substantially greater than those for distilled water and that the changes are approximately equal to the cell resting potential (60-90 mv). Furthermore, as can be seen in FIG. 7, the potential is directly related to the concentration of the carbonated water (the “stale” solution shows no bubbles while the “fresh” solution effervesces and deposits bubbles onto the skin). There was an increase in potential when the carbonated water was agitated which suggests that the decrease in potential with time arises in part from a CO 2 concentration gradient in the carbonated water. No change occurs when the distilled water is agitated.
  • the decrease in carbonated water potential with time can arise from a decrease in its CO 2 concentration due to CO 2 diffusion into the skin, from a concentration gradient within the solution, and from an increase in the CO 2 concentration in the skin.
  • the increase in potential upon agitation of the solution indicates that diffusion is primarily into the skin rather than into the atmosphere.
  • the CO 2 dose into the skin can be determined as a function of the decrease in the concentration of CO 2 in the agitated solution by various methods of measurement (e.g., conductivity, cell potential, pH or titration). By correlation of such measurements with the observed decrease in liquid/body potential, that decrease could be used as a convenient clinical method for dose determination.
  • the changes in distilled water potential can arise from changes in concentration of body fluids in the skin and in the applied liquid due to interdiffusion of the distilled water and the body fluid components, for example, by osmosis.
  • FIG. 8 shows data taken under the same conditions as those in FIG. 7 except that they are taken immediately after exercise. It can be seen that the potentials and associated changes with time are more than twice as large as those in FIG. 7 .
  • the data in FIG. 9, taken 15 minutes after those in FIG. 8, show a reversion to the behavior observed before exercise in FIG. 7 .
  • the application of CO 2 actually decreases the potential of the liquid applied on the skin in an adjacent region, whether that liquid is carbonated or distilled water.
  • liquid/body potential difference appears to be a quantitative measure of the concentration and delivered transcutaneous dose of CO 2 via carbonated water applied to the skin.
  • the ⁇ 3 minute exponential decay time of the liquid/body potential changes corresponds to the time for reddening of the skin by applied CO 2 and for the reddening of the skin to disappear, suggesting a 1:1 correlation of the observed potential and the physiological effects of CO 2 application.
  • a subject In therapeutic use, a subject would apply gaseous CO 2 to an affected area of the body. Application could be accomplished by a number of different apparatus.
  • a dispensing device 1000 such as that shown in U.S. patent applications Ser. Nos. 09/614,389 and 09/708,186 for infusion of the nose, mouth or eyes could be used to bathe the affected area in CO 2 .
  • the flow rate for the devices of U.S. patent application Ser. No. 09/614,389 is as low as 2 to 10 cc/sec, although higher flow rates are possible with the same device.
  • the user could place a hand 1010 over the area forming a pocket between the hand and the area of skin.
  • a cup 1100 or similar apparatus of appropriate size and shape could be used in conjunction with the source of CO 2 1110 to retain the gas over the treated area.
  • the cup would be of a gas impermeable material to limit the loss of CO 2 .
  • the funnel apparatus used in the inventors' experiment to measure the rate of transcutaneous absorption of CO 2 could also be used with minimal modifications to accomplish the same purpose. With the cup or funnel, after placement on the affected area, the cup or funnel would be purged of air by a prolonged flow of CO 2 . Unlike the experiment described previously, it would not be necessary to move the device after the purging procedure. The time of CO 2 application could vary from a few minutes to, if an attached cup or funnel device was used, a few hours.
  • the gas used for treatment should be essentially pure, that is, by volume, at least 50% carbon dioxide, preferably at least 70% carbon dioxide and more preferably 95% or greater.
  • gases other than CO 2 , drugs, surfactants or other substances could be incorporated into the flow.
  • an aqueous solution of CO 2 can be used to relieve both localized and general pain through submersion of the affected areas.
  • the general procedure would be to place fresh, carbonated water (not shown) into a container or tub 1200 of appropriate size and have the subject submerge the area(s) to be treated in the carbonated water, for example, the hand and wrist 1210 .
  • the subject could vary the time of submersion from a few minutes, preferably at least three minutes, to a few hours, depending upon the severity of the pain and individual response to the treatment.
  • Submersion of the whole body or substantially the whole body, i.e., the entire body except the head to allow for breathing, may be appropriate for certain treatments.
  • a device such as that used to test the subject response could be used.
  • the fresh, carbonated water 430 could be contained in a CO 2 “ patch,” for example an open container or cylinder 410 , and the container placed on the skin over an affected area.
  • the fresh carbonated water can be placed in a standard “squeeze” bottle 510 , such as is used for nasal spray, or a modification thereof.
  • a standard “squeeze” bottle 510 such as is used for nasal spray, or a modification thereof.
  • the subject would open the bottle, placed the bottle into a nostril or other orifice, and squeeze to produce a spray of the capnic solution. The bottle would then be closed tightly to preserve the carbonated water for later use.
  • FIG. 13 shows “patch” embodiments by which CO 2 or other gaseous agents can be applied to the skin to relieve pain in a region of the body.
  • FIG. A shows a patch 1300 with a peelable closure 1305 to contain and protect its active contents before use.
  • FIG. B shows the patch 1300 with the peelable closure removed and applied to the skin to relieve pain in a region of the body.
  • the patch 1300 consists of a cavity 1310 enclosed by a gas and liquid impermeable plastic envelope 1320 having an adhesive rim 1330 for attachment of the edge of the cavity to the skin 1335 , thereby forming a gas-tight seal and chamber 1340 .
  • the chamber 1340 is filled with a sponge or other liquid-containing medium 1350 soaked with a gas-containing liquid. When the patch is in use this liquid is in contact with the skin and delivers a dose of the dissolved gaseous agent to the underlying tissue by transcutaneous diffusion as describe herein.
  • An electrode 1360 can be used to monitor the dose and its effect on the tissue by measurement of the electrical potential between this electrode and a conventional ECG electrode (not shown) elsewhere on the body, as described and shown in connection with FIGS. 7-9.
  • a conventional ECG electrode not shown
  • an electrode as shown could be included for use in a clinical setting, it need not be a part of a patch intended solely for more general use.
  • the patch 1300 shown in FIGS. A and B the gas-containing liquid in the chamber 1340 can be replaced by an agent that generates the gas by a chemical reaction such as a mixture of solid citric acid and water-containing microcapsules, which when crushed together release a substantial quantity of carbon dioxide gas that then can diffuse through the skin as described.
  • an agent that generates the gas by a chemical reaction such as a mixture of solid citric acid and water-containing microcapsules, which when crushed together release a substantial quantity of carbon dioxide gas that then can diffuse through the skin as described.
  • a chemical reaction such as a mixture of solid citric acid and water-containing microcapsules
  • the chamber 1340 may include a porous envelope 1345 inside the gas and liquid impermeable envelope 1320 that contains the gas-generating agent 1355 to which water is added just prior to application of the patch 1300 to activate the gas generation process.
  • the skin would not need not be moistened prior to use of the patch.
  • a small cylinder 1370 containing the gaseous agent at low pressure is attached to the patch 1300 with a mechanism and port 1375 for its slow release into the patch chamber 1340 .
  • a vent 1380 for escape of air as air is purged from the patch and to prevent overpressure within the chamber.
  • Such a vent may be desirable in patch embodiments that utilize an agent for chemical generation of the gas.
  • the chamber 1340 could be filled with a carbonated or plain water-soaked sponge or similar medium similar to the medium 1310 , and gas from the attached cylinder would then used to maintain a high gas concentration in the water for long-term application.
  • the quantity of CO 2 required to achieve saturation of the skin is very small, so the required volume of carbonated water or gas-generating agent in the patch, or of gas in the cylinder, is easily contained in a conveniently-sized patch.
US09/795,648 2000-02-28 2001-02-28 Method and apparatus for transcutaneous infusion of carbon dioxide for local relief of pain and other ailments Expired - Lifetime US6652479B2 (en)

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US09/795,648 US6652479B2 (en) 2000-02-28 2001-02-28 Method and apparatus for transcutaneous infusion of carbon dioxide for local relief of pain and other ailments
US10/666,562 US20080132825A1 (en) 2000-02-28 2003-09-17 Transcutaneous infusion of carbon dioxide for local relief of pain and other ailments
US10/666,947 US20050228337A1 (en) 2000-02-28 2003-09-17 Transcutaneous infusion of carbon dioxide for local relief of pain and other ailments

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US18549500P 2000-02-28 2000-02-28
US09/795,648 US6652479B2 (en) 2000-02-28 2001-02-28 Method and apparatus for transcutaneous infusion of carbon dioxide for local relief of pain and other ailments

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US10/666,562 Division US20080132825A1 (en) 2000-02-28 2003-09-17 Transcutaneous infusion of carbon dioxide for local relief of pain and other ailments

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US10/666,562 Abandoned US20080132825A1 (en) 2000-02-28 2003-09-17 Transcutaneous infusion of carbon dioxide for local relief of pain and other ailments
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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050228337A1 (en) * 2000-02-28 2005-10-13 Capnia, Incorporated Transcutaneous infusion of carbon dioxide for local relief of pain and other ailments
US20050254993A1 (en) * 2002-07-01 2005-11-17 Masaya Tanaka Carbon dioxide external administration device
US20050279350A1 (en) * 1999-07-12 2005-12-22 Capnia Incorporated Methods and apparatus for relieving headaches, rhinitis and other common ailments
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US20080132825A1 (en) * 2000-02-28 2008-06-05 Capnia, Incorporated Transcutaneous infusion of carbon dioxide for local relief of pain and other ailments
US20110071461A1 (en) * 2002-07-01 2011-03-24 Masaya Tanaka Carbon dioxide external administration device
US20050254993A1 (en) * 2002-07-01 2005-11-17 Masaya Tanaka Carbon dioxide external administration device
US8079998B2 (en) * 2006-10-20 2011-12-20 Pulmonox Technologies Corporation Methods and devices for the delivery of therapeutic gases including nitric oxide
US20120118287A1 (en) * 2006-10-20 2012-05-17 Pulmonox Technologies Corporation Methods and devices for the delivery of therapeutic gases including nitric oxide
WO2009054501A1 (fr) 2007-10-25 2009-04-30 Neochemir Inc. Utilisation d'une unité d'alimentation en dioxyde de carbone pour le renforcement des muscles et procédé permettant d'augmenter ainsi la viande bovine
US20110046545A1 (en) * 2008-12-26 2011-02-24 Shoichi Nakamura Cover for gas mist pressure bath
US20110028888A1 (en) * 2008-12-26 2011-02-03 Shoichi Nakamura Cover for gas mist pressure bath
US8876748B2 (en) * 2008-12-26 2014-11-04 Acp Japan Co., Ltd. Cover for gas mist pressure bath
US9017278B2 (en) * 2008-12-26 2015-04-28 Acp Japan Co., Ltd. Cover for gas mist pressure bath
US11439553B2 (en) 2018-05-09 2022-09-13 André Hugo Smith Multimodal device for transdermal treatments

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EP1259282A4 (fr) 2007-05-23
US20050228337A1 (en) 2005-10-13
JP2004511263A (ja) 2004-04-15
US20080132825A1 (en) 2008-06-05
WO2001064280A1 (fr) 2001-09-07
US20020040205A1 (en) 2002-04-04
AU2001272086A1 (en) 2001-09-12
EP1259282A1 (fr) 2002-11-27

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